DNA Interaction, DNA Photocleavage, Photocytotoxicity In Vitro, and Molecular Docking of Naphthyl-Appended Ruthenium Complexes

Hu, Xia; Luo, Qian; Qin, Yao; Wu, Yao; Liu, Xue-wen

doi:10.3390/molecules27123676

Cited by 5 publications

(2 citation statements)

References 45 publications

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“…The ctDNA cleavage abilities of [RuNOTSP] + and TSPH 2 were measured using a diphenylamine assay. Generally, single-strand or double-strand breaks can convert the plasmid DNA from supercoil DNA to other forms of DNA [ 68 , 69 ]. The diphenylamine assay results are shown in Figure 12 .…”

Section: Resultsmentioning

confidence: 99%

DNA Binding and Cleavage, Stopped-Flow Kinetic, Mechanistic, and Molecular Docking Studies of Cationic Ruthenium(II) Nitrosyl Complexes Containing “NS4” Core

et al. 2023

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This work aimed to evaluate in vitro DNA binding mechanistically of cationic nitrosyl ruthenium complex [RuNOTSP]+ and its ligand (TSPH2) in detail, correlate the findings with cleavage activity, and draw conclusions about the impact of the metal center. Theoretical studies were performed for [RuNOTSP]+, TSPH2, and its anion TSP−2 using DFT/B3LYP theory to calculate optimized energy, binding energy, and chemical reactivity. Since nearly all medications function by attaching to a particular protein or DNA, the in vitro calf thymus DNA (ctDNA) binding studies of [RuNOTSP]+ and TSPH2 with ctDNA were examined mechanistically using a variety of biophysical techniques. Fluorescence experiments showed that both compounds effectively bind to ctDNA through intercalative/electrostatic interactions via the DNA helix’s phosphate backbone. The intrinsic binding constants (Kb), (2.4 ± 0.2) × 105 M−1 ([RuNOTSP]+) and (1.9 ± 0.3) × 105 M−1 (TSPH2), as well as the enhancement dynamic constants (KD), (3.3 ± 0.3) × 104 M−1 ([RuNOTSP]+) and (2.6 ± 0.2) × 104 M−1 (TSPH2), reveal that [RuNOTSP]+ has a greater binding propensity for DNA compared to TSPH2. Stopped-flow investigations showed that both [RuNOTSP]+ and TSPH2 bind through two reversible steps: a fast second-order binding, followed by a slow first-order isomerization reaction via a static quenching mechanism. For the first and second steps of [RuNOTSP]+ and TSPH2, the detailed binding parameters were established. The total binding constants for [RuNOTSP]+ (Ka = 43.7 M−1, Kd = 2.3 × 10−2 M−1, ΔG0 = −36.6 kJ mol−1) and TSPH2 (Ka = 15.1 M−1, Kd = 66 × 10−2 M, ΔG0 = −19 kJ mol−1) revealed that the relative reactivity is approximately ([RuNOTSP]+)/(TSPH2) = 3/1. The significantly negative ΔG0 values are consistent with a spontaneous binding reaction to both [RuNOTSP]+ and TSPH2, with the former being very favorable. The findings showed that the Ru(II) center had an effect on the reaction rate but not on the mechanism and that the cationic [RuNOTSP]+ was a more highly effective DNA binder than the ligand TSPH2 via strong electrostatic interaction with the phosphate end of DNA. Because of its higher DNA binding affinity, cationic [RuNOTSP]+ demonstrated higher cleavage efficiency towards the minor groove of pBR322 DNA via the hydrolytic pathway than TSPH2, revealing the synergy effect of TSPH2 in the form of the complex. Furthermore, the mode of interaction of both compounds with ctDNA has also been supported by molecular docking.

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Section: Resultsmentioning

confidence: 99%

DNA Binding and Cleavage, Stopped-Flow Kinetic, Mechanistic, and Molecular Docking Studies of Cationic Ruthenium(II) Nitrosyl Complexes Containing “NS4” Core

et al. 2023

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“…Molecular docking of previously reported ruthenium complexes in its different oxidation states (0, II, and III) showed variable binding affinities to the DNA. The score values varied between −9.0 and −5.0 according to the oxidation state of metal species [ 11 , 65 , 66 , 67 , 68 ]. Although the current ruthenium complex displayed a lesser S value, it was characterized by the presence of three H-bonding.…”

Section: Resultsmentioning

confidence: 99%

Molecular Design, Spectroscopic, DFT, Pharmacological, and Molecular Docking Studies of Novel Ruthenium(III)–Schiff Base Complex: An Inhibitor of Progression in HepG2 Cells

Noureldeen

Aziz

Shouman

et al. 2022

IJERPH

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A novel ruthenium(III)–pyrimidine Schiff base was synthesized and characterized using different analytical and spectroscopic techniques. Molecular geometries of the ligand and ruthenium complex were investigated using the DFT-B3LYP level of theory. The quantum global reactivity descriptors were also calculated. Various biological and molecular docking studies of the complex are reported to explore its potential application as a therapeutic drug. Cytotoxicity of the complex was screened against cancer colorectal (HCT116), breast (MCF-7 and T47D), and hepatocellular (HepG2) cell lines as well as a human normal cell line (HSF). The complex effectively inhibited the tested cancer cells with variable degree with higher activity towards HepG2 (IC50 values were 29 μM for HepG2, 38.5 μM for T47D, 39.7 μM for HCT, and 46.7 μM for MCF-7 cells). The complex induced apoptosis and cell cycle arrest in the S phase of HepG2 cells. The complex significantly induced the expression of H2AX and caspase 3 and caspase 7 gene and the protein level of caspase 3, as well as inhibited VEGF-A and mTOR/AKT, SND1, and NF-kB gene expression. The molecular docking studies supported the increased total apoptosis of treated HepG2 cells due to strong interaction of the complex with DNA. Additionally, the possible binding interaction of the complex with caspase 3 could be responsible for the elevated activity of caspase 3–treated cells. The score values for the two receptors were −3.25 and −3.91 kcal/mol.

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GSH-responsive and folate receptor-targeted pyridine bisfolate-encapsulated chitosan nanoparticles for enhanced intracellular drug delivery in MCF−7 cells

Elshami,

Elrefaei,

Ibrahim

et al. 2024

Carbohydrate Research

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DNA Interaction, DNA Photocleavage, Photocytotoxicity In Vitro, and Molecular Docking of Naphthyl-Appended Ruthenium Complexes

Cited by 5 publications

References 45 publications

DNA Binding and Cleavage, Stopped-Flow Kinetic, Mechanistic, and Molecular Docking Studies of Cationic Ruthenium(II) Nitrosyl Complexes Containing “NS4” Core

DNA Binding and Cleavage, Stopped-Flow Kinetic, Mechanistic, and Molecular Docking Studies of Cationic Ruthenium(II) Nitrosyl Complexes Containing “NS4” Core

Molecular Design, Spectroscopic, DFT, Pharmacological, and Molecular Docking Studies of Novel Ruthenium(III)–Schiff Base Complex: An Inhibitor of Progression in HepG2 Cells

GSH-responsive and folate receptor-targeted pyridine bisfolate-encapsulated chitosan nanoparticles for enhanced intracellular drug delivery in MCF−7 cells

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